ANTHELMINTIC FORMULATIONS

Abstract: This invention relates to anthelmintic compositions and has particular application to injectable compositions containing closantel together with an avermectin or milbemycin such as moxidectin, ivermectin, doramectin Milbemycin D, or other milbemycins together with a glycol based solvent such as polyethylene glycol or propylene glycol. The formulations may also include trace elements and/or vitamins.

Description: ANTHELMINTIC FORMULATIONS 5 FIELD This invention relates to veterinary compositions for the treatment of helminthiasis in warm-blooded animals, more particularly cattle, sheep, goats, and other domesticated herbivores. 10 BACKGROUND Helminthiasis is a widely occurring disease in farmed animals. It commonly causes clinical disease and has significant adverse economic effects on farming economies j r j when present at subclinical levels. Over the past twenty-five years a number of initially successful anthelmmtic agents, with relatively specific effects on the metabolism of smaller or larger groups of endoparasites have been discovered, trialled, and used successfully to control helminthiasis on farms. Various groups of compounds have a greater or lesser spectrum of activity - that is to say they are able to destroy a wider or smaller range of parasite. For example, the widely used "ivermectin" is active against parasitic roundworms and also against some ectoparasites, yet it is inactive against tapeworms because of a difference ih their biochemical constitution. "Triclabendazole" is active only against the liver fluke Fasciola hepatica. The drug closantel is a useful anthelmintic active agent that gives control over a range 25 of internal parasites including liverfluke in cattle and sheep. For this reason it has been used in aqueous suspension in combination with other anthelmintics such as albendazole and mebendazole. This invention is based on the surprising discovery that an anthelmintic solution can be prepared from a combination of closantel and an avermectin or milbemycin like 30 anthelmintic, for example ivermectin, moxidectin and doramectin. Such solutions have advantages in ease of use and may also be used by injection. Glycol based solvents such as polyethylene glycol and propylene glycol are able to dissolve both compounds to produce a stable formulation. Such formulations may also be dispersed in water. 35 The milbemycins are described in the 11th Edition of the Merck index as a family of novel macrolide antibiotics with Milbemycin D in particular being used as an anthelmintic. The avermectins are described in the 11th Edition of the Merck index as a group of broad-spectrum antiparasitic compounds which are derivatives of pentacyclic 16-membered lactones related to the milbemycins. The most well known of these avermectins is ivermectin which is a semi-synthetic derivative of abamectin (one of the avermectins). OBJECT It is an object of this invention to provide novel veterinary compositions having anthelmintic activity. STATEMENT OF INVENTION In one aspect the invention comprises a composition including an effective amount of the anthelmintic closantel together with a glycol based solvent and an effective amount of at least one other anthelmintic. In a further aspect the invention provides a method for treating helminthiasis in animals with compositions comprising an effective amount of the anthelmintic closantel together with a glycol based solvent and an effective amount of at least one other anthelmintic. Preferably the other anthelmintic is chosen from the group comprising the avermectins or milbemycins. Such a group includes moxidectin, ivermectin, doramectin, Milbemycin D, as well as other milbemycins. Preferably the compositions of the present invention are used by injection. They may also include trace elements and/or vitamins. Preferably the closantel and other anthelmintic may be each present at from 0.5 to 15% w/v respectively, and more preferably the closantel is present at from 1 to 2% w/v. In another aspect the invention provides a method of treating animals for helminthiasis by injecting a composition as previously described at the rate of lmL/50kg of the animal's live weight (different dose rates and percentages of active ingredients will become apparent from the examples). Preferably the closantel and other anthelmintic is dissolved in a mixture selected from at least two of: propylene glycol, polyethylene glycol, glycerol formal and water. EXAMPLES These and other aspects of the invention will be apparent from the following description, which is given by way of example only. This formulation is suitable for use as an oral drench for sheep which would offer control of parasites resistant to older anthelmintics such as the benzimidazoles and levamisole as well as controlling adult liverfluke. This formulation is suitable for use as an injection for sheep and cattle. It gives the advantage of longer action of moxidectin combined with activity against liverfluke. This is an injectable composition containing selenium. Preparation Example To a clean dry mixing vessel, add the glycerol formal (i) and Tween 80. With stirring, add the abamectin and sodium closantel, and heat to about 60" - 70 * C with continued stirring until dissolved. Dissolve the sodium selenate in water and add to the batch while stirring. Allow to cool to room temperature and add the benzyl alcohol, stirring well to disperse. Make up to 100% volume with glycerol formal (ii). Trial solutions of Example 3 were found to be stable overnight at 2 * C, 21 * C and 37°C with the active ingredients remaining soluble at all temperatures. Use This injectable formulation can be applied to cattle at a dose rate of lmL/50kg of live weight, to provide the animal with 2.5mg/kg of closantel whilst at the same time supplying an effective dose of abamectin and a trace element such as selenium. Example 4: Dose rate lml/50kg This provides another injectable formulation without the trace element by using a combination of polyethylene glycol (PEG 400) and glycerol formal. Examples 5 - 7 show other injectable compositions containing different amounts of closantel to be used at a formulation dose rate of 1 mL/25kg of animal live weight. Dose rate lml/25kg In addition to the combination of closantel and an avermectin or milbemycin the compositions of this invention can contain trace elements. Example 3 describes a composition containing selenium. Other trace elements or vitamins may be included. Examples of trace elements include copper, cobalt, iodine, zinc or the like. The vitamins may be for example vitamins A, B, D, or E. ADVANTAGES The compositions of this invention are stable and safe to use. The glycol based solvents used in this invention are non-irritant solvents and can safely be used in injectable compositions. The injectable compositions are particularly suited to the control of helminthiasis in cattle.

Claims: CLAIMS 1. A composition including an effective amount of the anthelmintic closantel together with a glycol based solvent and an effective amount of at least one other anthelmintic. 2. A composition as claimed in claim 1 wherein the other anthelmintic is selected from the group comprising the avermectins and milbemycins. 3. A composition as claimed in claim 2 wherein the avermectins and milbemycins are selected from the group comprising abamectin, ivermectin, moxidectin, doramectin and Milbemycin D. 4. A composition as claimed in any one of claims 1-3 wherein the closantel and other anthelmintic is dissolved in a solvent selected from the group comprising: propylene glycol, polyethylene glycol, glycerol formal and water. 5. A composition as claimed in claim 4 wherein the closantel and other anthelmintic are each present at from 0.5 to 15% w/v respectively. 6. An injectable formulation comprising a composition as claimed in any one of claims 1-5. 7. An injectable formulation comprising a composition as claimed in claim 6 wherein the closantel is present at from 1 to 2% w v. A composition as claimed in any one of claims 1 to 7 wherein the closantel and other anthelmintic is dissolved in a mixture selected from at least two of: propylene glycol, polyethylene glycol, glycerol formal and water. A method of treating animals for helminthiasis by injecting a composition as claimed in claim 7 at the rate of lmL/25kg to lmL/50kg of the animal's live weight.

Inventors: HARVEY COLIN MANSON, HARVEY, COLIN, MANSON
Applicants: ASHMONT HOLDINGS LTD, HARVEY COLIN MANSON, ASHMONT HOLDINGS LIMITED, HARVEY, COLIN, MANSON
Application year: 1994
Main classification: A61K31
IPC codes: A61K47